Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain

Abstract Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in ra...

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Veröffentlicht in:Journal of neuropathology and experimental neurology 2023-05, Vol.82 (5), p.419-426
Hauptverfasser: An, Min, Qiu, Yi, Wang, Caixia, Ma, Penglei, Ding, Yumei
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container_issue 5
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creator An, Min
Qiu, Yi
Wang, Caixia
Ma, Penglei
Ding, Yumei
description Abstract Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.
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The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlad006</identifier><identifier>PMID: 36779914</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Apoptosis ; Astrocytes ; Astrocytes - metabolism ; Cellular signal transduction ; Constriction ; Development and progression ; Guanosine triphosphatase ; Health aspects ; Inflammation ; MAP Kinase Signaling System ; Microglia - metabolism ; Neuralgia ; Neuralgia - etiology ; Neuralgia - metabolism ; Neurological research ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; Sirtuin 1 - pharmacology</subject><ispartof>Journal of neuropathology and experimental neurology, 2023-05, Vol.82 (5), p.419-426</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2023 Oxford University Press</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. 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subjects Animals
Apoptosis
Astrocytes
Astrocytes - metabolism
Cellular signal transduction
Constriction
Development and progression
Guanosine triphosphatase
Health aspects
Inflammation
MAP Kinase Signaling System
Microglia - metabolism
Neuralgia
Neuralgia - etiology
Neuralgia - metabolism
Neurological research
Rats
Rats, Sprague-Dawley
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Sirtuin 1 - pharmacology
title Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain
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